X-ray crystal structures and conformational analysis of cyclic acetals derived from tartaric acid and rigid spacer units

Article abstract of DOI:10.1007/s11224-011-9934-5

Three tartaric ester and tartaric acid derivatives (1-3) with the hydroxy groups being linked via cyclic acetal (1,3-dioxolane) formation to a rigid core, containing phenyl and ethynyl units, have been synthesized. Their crystal structures are reported, emphasizing the molecular geometry, intermolecular interactions, and the resulting packing motifs. All dioxolane rings present in the crystal structures of 1-3 are analyzed and compared with regard to their conformational behavior. In spite of similar substitution patterns, the dioxolane units adopt different conformations including twist and varying envelope isomers. The crystal structures are dominated by C- H···O (esters 1 and 2) and O-H···O (acid 3) hydrogen bonds, leading to different types of packing motifs being characteristic of strand and layer formation.

Full text of DOI:10.1007/s11224-011-9934-5

Struct Chem (2012) 23:1131–1142
DOI 10.1007/s11224-011-9934-5
ORIGINAL RESEARCH
X-ray crystal structures and conformational analysis of cyclic
acetals derived from tartaric acid and rigid spacer units
•
Diana Eißmann Felix Katzsch Edwin Weber
•
Received: 31 August 2011 / Accepted: 16 December 2011 / Published online: 17 January 2012
Ó Springer Science+Business Media, LLC 2012
Abstract Three tartaric ester and tartaric acid derivatives
(1–3) with the hydroxy groups being linked via cyclic
acetal (1,3-dioxolane) formation to a rigid core, containing
phenyl and ethynyl units, have been synthesized. Their
crystal structures are reported, emphasizing the molecular
geometry, intermolecular interactions, and the resulting
packing motifs. All dioxolane rings present in the crystal
structures of 1–3 are analyzed and compared with regard to
their conformational behavior. In spite of similar substi-
tution patterns, the dioxolane units adopt different con-
formations including twist and varying envelope isomers.
The crystal structures are dominated by C–HꢀꢀꢀO (esters 1
and 2) and O–HꢀꢀꢀO (acid 3) hydrogen bonds, leading to
different types of packing motifs being characteristic of
strand and layer formation.
complexation properties [2] giving rise to numerous
applications, especially in analytical fields such as a
masking agent [3] or for the detection of reducing sugars
[4]. In organic synthesis, tartrates are used as chiral aux-
iliaries, as resolving agents and for the synthesis of chiral
building blocks. [5–7] Out of three possible stereoisomers,
the natural L(?)-tartaric acid is the most common and is
therefore readily available in its enantiopure form.
Molecules, the crystal structures of which are reported
in this article, were designed in order to use them or their
corresponding carboxylic acids as tectons for the formation
of non-covalent organic frameworks (NoCOFs) or as
linkers for metal organic framework (MOF) synthesis. [8,
9] Hence, molecular structures are supposed to contain a
rigid core (phenyl and ethynyl units) as well as carboxylic
acid functions in order to assemble via hydrogen bonding
or to coordinate with metal ions. Following this line, chiral
tartaric acid moieties attached to the phenyl ring of the
rigid core by a transacetalization reaction, giving rise to a
cyclic acetal (1,3-dioxolane), are promising molecular
structures. While several tartaric acid and tartaric ester-
derived dioxolanes with varying substitution patterns have
been described in the literature [10–12], the compounds
presently studied in this article have not been reported
before.
Keywords Tartaric acid derivatives ꢀ Dioxolane ꢀ
Conformational analysis ꢀ X-ray analysis ꢀ Hydrogen
bonding
Introduction
Tartaric acid is one of the most important natural
a-hydroxycarboxylic acids, being in the form of its sodium
ammonium salt the first compound that was separated into
its enantiomeric forms by Pasteur [1]. Furthermore, tartaric
acid and its derivatives are known for their outstanding
Here, we present the synthesis and the results of X-ray
crystal structure analyses of diethyl tartrate derivatives 1
and 2 as well as tartaric acid derivative 3 (Fig. 1) laying
emphasis on the modes of crystal packing, types of inter-
molecular interactions and the molecular structures. Since
all three compounds consist of one or two dioxolane
moieties, it is quite obvious to make a comparison with
regard to the conformational behavior including crystal
structures of similar dioxolanes [13–16], which is also a
subject of this study.
D. Eißmann ꢀ F. Katzsch ꢀ E. Weber (&)
¨
Institut fu¨r Organische Chemie, Technische Universitat
Bergakademie Freiberg, Leipziger Str. 29, 09596 Freiberg,
Sachsen, Germany
e-mail: edwin.weber@chemie.tu-freiberg.de
123

1132
Struct Chem (2012) 23:1131–1142
EtOOC
EtOOC
Fig. 1 Chemical structures of
target molecules 1, 2, and 3
EtOOC
EtOOC
COOEt
COOEt
HOOC
O
O
O
O
O
O
O
COOH
O
HOOC
1
2
3
EtO
Fig. 2 Synthetic route to
tartaric acid derivatives
1, 2, and 3
EtO
EtO
COOEt
Br
EtO
7
4
1. MEBYNOL, A
2. NaH, toluene
B
EtO
EtO
EtOOC
O
A
COOEt
5
O
EtOOC
EtO
EtO
OEt
OEt
8
B
6
1. LiOH, THF
2. HCl
B
1
2
3
A: Pd(PPh3)2Cl2, CuI, PPh3, Et3N
B: L(+)-DET, PyrTos, toluene
Experimental
degassed triethylamine (20 mL). To this solution, the cata-
lyst [composed of Pd(PPh3)Cl2 (6.7 mg, 0.0095 mmol), CuI
(6.5 mg, 0.034 mmol), and PPh3 (12.5 mg, 0.048 mmol)]
was added and the mixture was stirred at 110 °C under argon
for 9 h. The suspension was diluted with diethyl ether and
washed with aqueous NH4Cl and NaCl solutions. After
drying over Na2SO4, the solvent was removed under reduced
pressure. The intermediate protected alkyne was obtained as
a brownish-red liquid. For cleavage of the protecting group,
toluene (p.a., 50 mL) and NaH (60% suspension in paraffin
oil, 0.26 g, 2.6 mmol) were added and the mixture was
refluxed for 16 h. Then dichloromethane (50 mL) was added
and the mixture was filtered. The filtrate was washed with
aqueous Na2CO3 and NaCl solutions. The organic layer
was dried over Na2SO4 and the solvent removed under
reduced pressure to yield 95% alkyne 4 as a brownish-red
liquid. Rf (EtOAc/n-hexane 1:4) = 0.78. 1H NMR (CDCl3,
A summary of the synthetic routes of compounds 1–3 is
given in Fig. 2.
General remarks
¨
Melting points were measured on a BUCHI Melting Point
¨
B-450 (BUCHI Labortechnik AG, Flawil, Switzerland).
1H NMR and 13C NMR spectra (ppm) were recorded on
a Bruker DPX 400 (400.1 and 100.6 MHz, respectively)
and a Bruker Avance III 500 (500.1 and 125.8 MHz,
respectively) using TMS as reference. IR spectra were
obtained from a Nicolet FT-IR 510 spectrometer as liquid
films in a NaCl cell or as KBr pellets. Optical rotation
measurements were performed on a Perkin-Elmer 241
polarimeter at 20 °C and with k = 589.3 nm (NaD line).
20
The ½aꢁD values are given in [deg mL dm-1 g-1].
3
400.1 MHz) d: 1.23 (t, JHH = 7.0 Hz, 6H, CH3); 3.07 (s,
Commercial chemicals [p-bromobenzaldehyde diethy-
lacetal (4), MEBYNOL, pyridinium tosylate] and solvents
were used without further purification.
1H, C:CH); 3.56 (m, 4H, CH2); 5.50 (s, 1H, CH); 7.43, 7.48
3
(2 d, JHH = 8.0 Hz, 2H, aryl-H). 13C NMR (CDCl3,
100.6 MHz) d: 15.1 (CH3); 61.0 (CH2); 77.3 (C:CH); 83.5
(C:CH); 100.9 (CH); 122.0, 126.6, 131.9, 139.8 (aryl-C).
IR (liquid film, cm-1) m: 3289; 2978; 2931; 2879; 2359;
4-Ethynylbenzaldehyde diethylacetal (5)
ꢀ
2109; 1925; 1706; 1608; 1565; 1445; 1392; 1337; 1211;
1174; 1115; 1094; 1054; 847; 816. GC–MS: m/z = 204
[M]?.
4-Bromobenzaldehyde diethylacetal (4) (5.00 g, 19.3 mmol)
and MEBYNOL (1.91 g, 22.7 mmol) were dissolved in
123

Struct Chem (2012) 23:1131–1142
1133
8H, aryl-H). 13C NMR (CDCl3, 100.6 MHz) d: 14.1 (CH3);
62.1 (CH2); 77.4, 77.7 (CH); 89.8 (C:C); 106.3 (CH);
124.7, 127.2, 131.6, 135.7 (aryl-C); 169.3 (C=O). IR (KBr,
4,40-Bis(diethoxymethyl)tolane (6)
4-Bromobenzaldehyde
diethylacetal
(4)
(19.02 g,
cm-1) m: 3066; 2987; 2933; 2898; 2873; 2360; 2224; 1761;
73.4 mmol), 4-ethynylbenzaldehyde diethylacetal (5)
(15.00 g, 73.4 mmol), triethylamine (75 mL), Pd(PPh3)2Cl2
(25.2 mg, 0.036 mmol), CuI (24.7 mg, 0.130 mmol), and
PPh3 (47.6 mg, 0.181 mmol) were reacted under the coupling
conditions as given above and worked up correspondingly to
obtain 31% of 6 as a colorless solid after recrystallization
from ethanol/acetone (1:1). Mp. 72–74 °C. Rf (EtOAc/
n-hexane 1:4) = 0.71. 1H NMR (CDCl3, 400.1 MHz) d: 1.24
ꢀ
1742; 1613; 1562; 1521; 1439; 1416; 1401; 1369; 1350;
1302; 1255; 1220; 1195; 1100; 1036; 995; 960; 945; 850;
824. ESI–MS: m/z = 633.0 [M?Na]?.
2-(p-Ethynylphenyl)-(4R,5R)-4,5-di(ethoxycarbonyl)-
1,3-dioxolane (2)
3
(t, JHH = 7.0 Hz, 12H, CH3); 3.58 (m, 8H, CH2); 5.52 (s,
3
p-Ethynylbenzaldehyde
diethylacetal
(5)
(4.50 g,
2H, CH); 7.46, 7.52 (2 d, JHH = 8.4 Hz, 2H, aryl-H). 13C
0.025 mol), L(?)-diethyl tartrate (5.00 g, 0.027 mol),
pyridinium tosylate (0.23 g, 1.0 mmol), and toluene (p.a.,
180 mL) were used to yield 50% of 1 as a yellow oil after
column chromatography (SiO2, EtOAc/n-hexane 1:4) which
crystallized on cooling to 0 °C. Mp. 55–59 °C. Rf (EtOAc/
NMR (CDCl3, 100.6 MHz) d: 15.2 (CH3); 61.0 (CH2); 89.4
(C:C); 101.0 (CH); 123.1, 126.7, 131.4, 139.2 (aryl-C). IR
(KBr, cm-1) m: 3053; 2971; 2923; 2908; 2873; 2363; 1932;
ꢀ
1717; 1613; 1565; 1518; 1483; 1451; 1442; 1388;1372; 1363;
1340; 1306; 1277; 1207; 1122; 1097; 1059; 1033; 1002; 960;
919; 875; 850; 805. GC–MS: m/z = 382 [M]?.
20
n-hexane 1:4) = 0.44. ½aꢁD (CHCl3, c = 0.01 mol L-1) =
1
-7.2. H NMR (CDCl3, 500.1 MHz) d: 1.30, 1.35 (2 t,
3JHH = 7.15 Hz, 3H, CH3); 3.11 (s, 1H, CH); 4.27, 4.33 (2 t,
3
3JHH = 7.15 Hz, 2H, CH2,); 4.83, 4.94 (2 d, JHH
=
Ethyl p-(diethoxymethyl)benzoic acid (7)
3.95 Hz, 1H, CH); 6.16 (s, 1H, CH); 7.51–7.56 (m, 4H, aryl-
H). 13C NMR (CDCl3, 125.8 MHz) d: 14.0, 14.1 (CH3); 62.1,
62.1 (CH2); 77.3, 77.7 (CH); 78.0, 83.2 (C:C); 106.1 (CH);
123.7, 127.1, 132.1, 136.1 (aryl-C); 168.9, 169.5 (C=O). IR
The compound was obtained in 91% yield as a yellow
liquid by acetalization and esterification of 4-formylben-
zoic acid with thionyl chloride and HC(OEt)3 in ethanol
according to the literature procedure [17]. Rf (EtOAc/
n-hexane 1:4) = 0.65. Spectroscopic and other analytical
data correspond to the literature specifications.
(KBr, cm-1) m: 3690; 3294; 3275; 3231; 3069; 2984; 2939;
ꢀ
2911; 2879; 2100; 1749; 1730; 1505; 1477; 1445; 1397;
1347; 1369; 1302; 1252; 1236; 1214; 1176; 1157; 1122;
1071; 1059; 1033; 979; 964; 951; 935; 865; 827; 764; 726.
GC–MS: m/z = 317 [M-H]?.
Tartaric acid derivatives 1, 2, and 8 (general procedure)
To a solution of the corresponding diethoxy acetal and
L(?)-diethyl tartrate in toluene (p.a.), a catalytic amount of
pyridinium tosylate was added. In order to remove the
by-product ethanol from the mixture, the solvent was dis-
tilled off during the reaction. The residue was diluted with
diethyl ether and washed with borax and water to remove
unreacted L(?)-diethyl tartrate. After drying over Na2SO4,
the solvent was removed under reduced pressure.
2-[(p-Ethoxycarbonyl)phenyl]-(4R,5R)-4,5-
di(ethoxycarbonyl)-1,3-dioxolane (8)
Ethyl p-(diethoxymethyl)benzoic acid (7) (6.00 g, 23.8 mmol),
L(?)-diethyl tartrate (5.40 g, 26.2 mmol), pyridinium tos-
ylate (0.24 g, 0.99 mmol) and toluene (p.a., 200 mL) were
used to yield 71% of 8 as a yellow oil after column chro-
matography (SiO2, EtOAc/n-hexane 1:4). Rf (EtOAc/
20
n-hexane 1:4) = 0.36. ½aꢁD (CHCl3, c = 0.01 mol L-1) =
1
2,20-(Tolane-4,40-diyl)bis[(4R,5R)-4,5-di(ethoxycarbonyl)-
1,3-dioxolane] (1)
-10.1. H NMR (CDCl3, 500.1 MHz, ppm) d: 1.30, 1.36,
1.40 (3 t, 3JHH = 7.15 Hz, 3H, CH3); 4.26, 4.33, 4.38 (3 q,
3
3JHH = 7.15 Hz, 2H, CH2); 4.85, 4.97 (2 d, JHH
=
4,40-Bis(diethoxymethyl)tolane (6) (2.00 g, 5.2 mmol),
L(?)-diethyl tartrate (2.37 g, 11.5 mmol), pyridinium tos-
ylate (0.11 g, 0.4 mmol), and toluene (p.a., 100 mL) were
used to yield 40% of 1 as a colorless solid after column
chromatography (SiO2, EtOAc/n-hexane 1:2). Mp 74–
3.90 Hz, 1H, CH,); 6.21 (s, 1H, CH); 7.67, 8.07 (2 d,
3
3JHH = 8.20 Hz, JHH = 8.40 Hz, 2H, aryl-H). 13C NMR
(CDCl3, 125.8 MHz, ppm) d: 14.0, 14.1, 14.2 (CH3); 61.0,
62.0, 62.0 (CH2); 77.3, 77.6, 105.8 (CH); 127.0, 129.5,
131.7, 140.1 (aryl-C); 166.1, 168.8, 169.3 (COOEt). IR
(liquid film, cm-1) m: 2984; 2941; 2907; 2873; 1756; 1719;
20
ꢀ
77 °C. Rf (EtOAc/n-hexane 1:2) = 0.31. ½aꢁD (CHCl3, c =
0.01 mol L-1) = ?19.0. 1H NMR (CDCl3, 400.1 MHz) d:
1.31 (m, 12H, CH3); 4.31 (m, 8H, CH2); 4.83, 4.95 (2 d,
3JHH = 4.0 Hz, 2H, CH); 6.17 (s, 2H, CH); 7.54–7.59 (m,
1617; 1580; 1513; 1470; 1445; 1430; 1393; 1365; 1279;
1214; 1174; 1103; 1020; 956; 857; 771; 706. GC–MS:
m/z = 365 [M-H]?.
123

1134
Struct Chem (2012) 23:1131–1142
2-(p-Carboxyphenyl)-(4R,5R)-4,5-dicarboxyl-1,3-
dioxolane (3)
C(9), C(10) in 3]. Geometrical calculations were performed
using PLATON [23] and molecular graphics were gener-
ated using SHELXTL [20].
A solution of the ester 7 (0.50 g, 1.36 mmol) and LiOH
(0.19 g, 8.19 mmol) in THF (25 mL) and H2O (10 mL) was
stirred at room temperature for 5 h. The reaction mixture was
diluted with water, acidified with 1 M HCl and repeatedly
extracted with diethyl ether. After washing the combined
organic extracts with water and drying it over Na2SO4, the
solvent was removed under reduced pressure. The obtained
crude product was purified by stirring it in cold dichloro-
methane to yield 66% of 3 as a colorless solid. Mp. 203–
Results and discussion
The crystals of 1 and 2 were found to be free of solvent,
while 3 was analyzed to contain water in a 1:1 (3:H2O)
stoichiometric ratio enclosed in the crystal. Crystal data
and details of the structure refinement are summarized in
Table 1. Geometric parameters of intermolecular interac-
tions of the compounds studied are listed in Table 2, while
Table 3 summarizes selected interplanar angles in the
crystal structure of compound 2. A conformational com-
parison of the dioxolane moieties in compounds 1–3 and in
similar derivatives described in the literature [13–16] is
given in Tables 4 and 5. Figure 3 shows the molecular
structures (ellipsoid plots) with atom labelling schemes,
while packing illustrations and specific patterns of inter-
molecular contacts are given in Figs. 4, 5, 6, and 7.
20
206 °C (dec). ½aꢁD (EtOH, c = 0.01 mol L-1) = -20.6. 1H
3
NMR (DMSO-d6, 500.1 MHz) d: 4.79, 4.94 (2 d, JHH
=
4.00 Hz, 3JHH = 3.90 Hz, 1H, CH); 6.08 (s, 1H, CH); 7.69,
3
3
7.99 (2 d, JHH = 8.15 Hz, JHH = 8.10 Hz, 2H, aryl-H);
13.63 (br s, 3H, COOH). 13C NMR (DMSO-d6, 125.8 MHz)
d: 76.9, 77.3, 104.5 (CH); 127.5, 129.3, 132.1, 140.7 (aryl-
C); 167.0, 170.5, 171.0 (COOH). IR (KBr, cm-1) m: 3120;
ꢀ
2670; 2550; 1755; 1685; 1581; 1515; 1426; 1391; 1223;
1100; 1043; 1017; 986; 951; 881; 856; 789; 770; 729 ESI–
MS: m/z = 281.03 [M-H]-.
Crystal structure of tartaric ester 1
Crystal structure determination
The compound crystallizes as colorless needles in the
monoclinic space group P21 with one molecule of 1 in the
asymmetric unit (Fig. 3). The packing is predominantly
stabilized by weak C–HꢀꢀꢀO [24, 25] and C–Hꢀꢀꢀp contacts
[26, 27]. With the dioxolane moiety as the hydrogen donor
and the carbonyl oxygen atom as the acceptor, molecules
are forced into chains (A and B) along the b axis with a
parallel alignment regarding the [503]-plane (Fig. 4). The
interplanar twist angle between the phenyl rings of both
chains is 58.3°, and between the phenyl rings and the
[503]-plane, the interplanar angels are 29.4° and 31.4°
(chains A and B, respectively). As illustrated in Fig. 4b,
adjacent chains are linked by an inverse bifurcated C–HꢀꢀꢀO
contact between a phenyl ring (hydrogen donor) and
dioxolane as well as carbonyl moieties (hydrogen accep-
tors). Weak C–Hꢀꢀꢀp contacts can be observed with aryl or
ethyl groups as hydrogen donors. Moreover, strands which
show an ABAB-alignment of adjacent chains are con-
nected by C–HꢀꢀꢀO contacts between two ester moieties.
Crystals of 1–3 suitable for X-ray analysis were obtained
by slowly cooling a hot solution of 1 in EtOH, cooling the
oily sample of 2 to 0 °C and slowly evaporating a solution
of 3 in Et2O/THF (1:1).
The X-ray diffraction intensities were recorded on a
Bruker Kappa diffractometer equipped with an APEX II
CCD area detector and graphite-monochromatized MoKa
˚
radiation (k = 0.71073 A) employing u and x scan modes.
The data were corrected for Lorentz and polarization
effects. The SAINT program [18] was utilized for inte-
gration of the diffraction profiles. For compound 3
(anisotropic crystal shape), a semiempirical absorption
correction was applied using the SADABS program [19].
The crystal structures were solved by direct methods and
refined by full-matrix least-squares refinement against F2
using SHELXL-97 [20]. All non-hydrogen atoms were
refined anisotropically; hydrogen atoms were generated at
ideal geometrical positions and refined with the appropriate
riding model or positioned by difference Fourier synthesis.
Because of the high uncertainty of the absolute parameter
x (FLACK) [21, 22] in the CIF file, the final refinement
steps of 1–3 were carried out by using the MERG 4 option
in SHELXL-97. The absolute configuration at the asym-
metry centers of the products is determined by the chirality
of the used stereoisomer of tartaric acid. So the molecules
have (R)-configuration at all chirality centers [C(9), C(10),
C(25), C(26) in 1, C(9), C(10), C(9A), C(10A) in 2 and
Crystal structure of tartaric ester 2
By cooling an oily sample of 2 to about 0 °C, colorless
crystals, showing the monoclinic space group P21 with two
molecules of 2 in the asymmetric unit (Fig. 3), were
obtained. The packing of molecules 1 (C1–C17, O1–6) and
2 (C1A–C17A, O1A–6A) can be described as layers par-
allel to the [101]-plane with an ABA0B0-pattern. Layers A
and A0 both consist of type 1 molecules, which are aligned
123

Struct Chem (2012) 23:1131–1142
1135
Table 1 Crystallographic data
for the compounds studied
Compound
1
2
3ꢀH2O
Empirical formula
Formula weight (g mol-1
C32H34O12
610.59
C17H18O6
318.31
C12H10O8ꢀH2O
300.22
)
Temperature (K)
153(2)
153(2)
153(2)
˚
Wavelength (A)
0.71073
0.71073
0.71073
Crystal system, space group
Unit cell dimensions
Monoclinic, P21
Monoclinic, P21
Monoclinic, P21
˚
a (A)
15.7607(9)
5.5507(4)
17.8716(11)
90
8.2434(2)
15.9061(4)
12.4178(3)
90
4.7386(1)
11.0661(3)
12.2429(3)
90
˚
b (A)
˚
c (A)
a (°)
b (°)
c (°)
108.528(3)
90
104.349(1)
90
91.705(2)
90
3
˚
V (A )
1482.42(16)
2
1577.43(7)
4
641.71(3)
2
Z
Calculated density (g cm-3
)
1.368
1.340
1.554
Absorption coefficient (mm-1
)
0.105
0.102
0.137
F(000)
Crystal size (mm3)
644
672
312
0.34 9 0.06 9 0.02
2.08–27.50
-20 B h B 20
-6 B k B 7
-23 B l B 23
30120/3767
[R(int) = 0.0599]
99.9
0.50 9 0.23 9 0.18
2.12–27.50
-10 B h B 10
-20 B k B 20
-16 B l B 16
30539/3754
[R(int) = 0.0350]
99.9
0.30 9 0.30 9 0.04
2.48–30.00
-6 B h B 6
-15 B k B 15
-17 B l B 17
16395/1959
[R(int) = 0.0243]
99.9
h Range for data collection (°)
Limiting indices
Reflections collected/unique
Completeness to h (%)
Data/restraints/parameters
Goodness-of-fit on F2
R indices [I [ 2r(I)]
3767/0/401
1.018
3754/1/419
1.041
1959/1/204
1.066
R1 = 0.0413,
wR2 = 0.0813
R1 = 0.0643,
wR2 = 0.0881
0.468/-0.274
R1 = 0.0296,
wR2 = 0.0726
R1 = 0.0326,
wR2 = 0.0742
0.214/-0.223
R1 = 0.0283,
wR2 = 0.0744
R1 = 0.0325,
wR2 = 0.0768
0.310/-0.162
R indices (all data)
-3
˚
Dqmax/Dqmin (e A
)
in opposite directions. In the same way, layers B and B0 are
formed by molecules of type 2. Interplanar angles involv-
ing the aromatic units facing one another and also the
[101]-plane are summarized in Table 3. Similar to the
crystal structure of 1, the packing of 2 is stabilized by
C–HꢀꢀꢀO and C–Hꢀꢀꢀp contacts. Within one layer of mole-
cules, the terminal alkyne group serves as a hydrogen bond
donor [28] and the carbonyl oxygen as the corresponding
acceptor site (Fig. 5). Furthermore, C–Hꢀꢀꢀp contacts
between ethyl hydrogen atoms and the p-system of alkyne
moieties can be observed. Intermolecular contacts between
dioxolane units (donor) and carbonyl oxygen atoms
(acceptor) as well as between two edge-to-face assembled
phenyl rings [29] connect layers A and B. The linkage
between layers A and B0 is formed by C–HꢀꢀꢀO (donor:
phenyl and dioxolane, acceptor: carbonyl) and C–Hꢀꢀꢀp
contacts (donor: phenyl, acceptor: alkyne). With dioxolane
being both hydrogen donor and acceptor, interactions
between layers A0 and B are formed. While the alkyne
moiety is involved in several intermolecular contacts in the
crystal structure of 2, no similar interactions have been
observed in the packing of compound 1.
Crystal structure of tartaric acid derivative 3
Compound 3 crystallizes as a monohydrate in the
monoclinic space group P21 with one molecule of 3 and
one water molecule in the asymmetric unit (Fig. 3).
Molecules are arranged in wavelike layers extending
parallel to the [102]-plane with an inclination angle of
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Struct Chem (2012) 23:1131–1142
˚
Table 2 Geometric parameters
of intermolecular interactions of
the compounds studied
Compounds
Atoms involved
Symmetry
Distance (A)
Angle (°)
D–HꢀꢀꢀA
DꢀꢀꢀA
HꢀꢀꢀA
1
C3–H3ꢀꢀꢀO11
-x, 1/2 ? y, 1 - z
-x, -1/2 ? y, -z
-x, -1/2 ? y, -z
x, 1 ? y, z
3.557(3)
3.402(3)
3.489(3)
3.311(4)
3.560(3)
3.560(4)
3.029(3)
3.439(3)
3.726(7)
3.559(7)
3.450(8)
3.593(6)
3.246(2)
3.252(2)
3.305(2)
3.347(2)
3.244(2)
3.155(2)
3.424(2)
3.710(8)
3.696(6)
3.588(2)
3.784(3)
2.808(2)
2.996(2)
2.874(2)
2.705(2)
2.557(2)
2.598(2)
3.249(2)
3.225(2)
2.68
2.66
2.60
2.51
2.62
2.59
2.56
2.68
3.00
2.73
2.71
2.75
2.30
2.33
2.37
2.36
2.50
2.43
2.53
2.85
2.82
2.87
2.83
1.93(5)
2.20(4)
2.59
1.87
1.75(4)
1.77
2.29
2.39
153
135
156
137
158
170
108
134
135
141
135
143
171
164
167
170
131
129
150
151
154
130
163
161(4)
160(4)
101
173
163(3)
167
160
141
C7–H7ꢀꢀꢀO1
C7–H7ꢀꢀꢀO3
C10–H10ꢀꢀꢀO5
C15–H15BꢀꢀꢀO6
C14–H14CꢀꢀꢀO10
C26–H26ꢀꢀꢀO9
C29–H29BꢀꢀꢀO9
C6–H6ꢀꢀꢀCg1a
1 - x, -1/2 ? y, -z
-x, -1/2 ? y, -z
x, -1 ? y, z
-1 - x, -1/2 ? y, 1 - z
-x, -1/2 ? y, -z
-x, -1/2 ? y, -z
-x, 1/2 ? y, 1 - z
-x, 1/2 ? y, 1 - z
2 - x, -1/2 ? y, 1 - z
2 - x, -1/2 ? y, 2 - z
2 - x, -1/2 ? y, 2 - z
x, -1 ? y, z
C13–H13BꢀꢀꢀCg2a
C20–H20ꢀꢀꢀCg2a
C31–H31BꢀꢀꢀCg1a
C17–H17ꢀꢀꢀO3
C17A–H17BꢀꢀꢀO3A
C4–H4ꢀꢀꢀO3A
2
C9A–H9AꢀꢀꢀO5
C10–H10ꢀꢀꢀO5A
C10A–H10AꢀꢀꢀO1
C13–H13AꢀꢀꢀO3A
C3–H3ꢀꢀꢀCg2b
1 - x, 1/2 ? y, 2 - z
2 - x, 1/2 ? y, 2 - z
x, 1 ? y, z
2 - x, 1/2 ? y, 2 - z
2 - x, -1/2 ? y, 1 - z
2 - x, 1/2 ? y, 2 - z
2 - x, -1/2 ? y, 1 - z
2 - x, -1/2 ? y, 1 - z
2 - x, -1/2 ? y, 2 - z
2 - x, -1/2 ? y, 2 - z
x, - 1 ? y, z
C4A–H4AꢀꢀꢀCg3b
C15–H15AꢀꢀꢀCg1b
C15–H15DꢀꢀꢀCg2b
O1G–H1GꢀꢀꢀO7
O1G–H2GꢀꢀꢀO7
O8–H8AꢀꢀꢀO2
3
a
Cg1, centroids of atoms
C2–C7 (phenyl); Cg2, centroids
of atoms C18–C23 (phenyl)
O8–H8AꢀꢀꢀO5
O4–H4ꢀꢀꢀO1G
1 - x, 1/2 ? y, 2 - z
2 - x, 1/2 ? y, 2 - z
x, 1 ? y, z
b
Cg1, centroids of atoms C1,
O6–H6AꢀꢀꢀO3
C17 (alkyne); Cg2, centroids of
atoms C1A, C17A (alkyne);
Cg3, centroids of atoms
C2–C7 (phenyl)
C9–H9ꢀꢀꢀO2
C10-H10ꢀꢀꢀO1G
2 - x, -1/2 ? y, 1 - z
regarded as a linkage element, supporting the stability of
the crystal structure by forming strong O–HꢀꢀꢀO hydrogen
bonds and weaker C–HꢀꢀꢀO contacts. This leads to an
assembly of three molecules of 3 and two water mole-
cules, giving rise to a cyclic hydrogen bond motif which
is illustrated in Fig. 7.
Table 3 Interplanar angles (°) between phenyl units of layers A, B,
A0, B0 and the [010]-plane
A/[010] A0/[010] B/[010] B0/[010] A/A0 B/B0 A/B A/B0
56.9
56.9
50.3
50.3
66.3 79.3 73.0 8.2
23.5° between the aromatic rings of adjacent molecules
(Fig. 6). In contrast to the crystal structures of compounds
1 and 2, the packing of 3 is stabilized by strong O–HꢀꢀꢀO
hydrogen bonds. Within the molecular layer, interactions
between two carboxylic moieties can be observed. How-
ever, no carboxylic acid dimers [30–32], being a strong
supra-molecular synthon [33, 34], is formed although the
carboxylic acid groups serve as hydrogen bond donor and
acceptor sites. On the contrary, the crystal water can be
Conformational analysis of the molecular structures
of 1, 2, and 3
As the tartaric acid derivative 1 features two independent
dioxolane units, attached to a tolane spacer, and the
asymmetric unit of 2 contains two non-equivalent mole-
cules, there are five dioxolane moieties whose conforma-
tional features in the solid state can be compared.
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Struct Chem (2012) 23:1131–1142
1137
Table 4 Conformational
comparison of 1, 2, and 3 with
similar dioxolane derivatives
described in the literature
(CSD acronyms)
Compound
Substitution pattern
1
Pucker parameter (CP)
Conformation
R5
5
O
(CSD acronym)
Q
u
(Atoms out of plane)
2
R2
O
4
R4
3
1
R2 = R0tolanyl
R4 = COOEt
trans 0.383(3)
194.7(4)
207.0(4)
Twist
0.376(3)
Envelope (C, position 2)
R5 = COOEt
2
R2 = p-ethynylphenyl
R4 = COOEt
trans 0.355(2)
289.8(3)
291.9(3)
Envelope (C, position 4)
Envelope (C, position 4)
0.315(2)
R5 = COOEt
3
R2 = carboxyphenyl
R4 = COOH
trans 0.354(2)
217.4(2)
165.5(6)
50.8(5)
24.8(8)
Envelope (C, position 2)
R5 = COOH
DUDFOY [40]
FOWZEX [41]
VOJGAD [13]
VOQLIX [14]
R2 = m-methoxyphenyl trans 0.308(3)
R4 = CONH2
Twist
Twist
Twist
R5 = CONH2
R2 = p-chlorophenyl
R4 = CONH2
trans 0.353(3)
trans 0.376(5)
R5 = CONH2
R2 = o-fluorophenyl
R4 = CONH2
R5 = CONH2
R2 = o-bromophenyl
R4 = CONH2
trans 0.335(10)
206.0(18)
44.3(14)
Twist
0.395(10)
Envelope (C, position 2)
R5 = CONH2
WEGXOW [15] R2 = dibenzofurane
R4 = COO-i-Pr
trans 0.409(5)
212.0(7)
Envelope (C, position 2)
Envelope (C, position 2)
0.220(5)
214.3(14)
R5 = COO-i-Pr
XEYSEA [16]
R2 = phenyl
R4 = COOEt
R5 = COOEt
trans 0.386(6)
59.2(9)
Twist
0.290(6)
177.2(11)
Envelope (O, position 1)
Table 5 Interplanar angles (°)
between mean planes of
dioxolane rings (A) and
Compound
Plane A
(atoms involved)
Plane B
(atoms involved)
Interplanar
angle (°) A/B
adjacent phenyl moieties (B)
1
(dioxolane 1)
(dioxolane 2)
2
(O1, O2, C8–C10)
(O7, O8, C24–C26)
(C2–C7)
72.7
27.2
(C18–C23)
(molecule 1)
(molecule 2)
3
(O1, O2, C8–C10)
(C2–C7)
54.3
45.2
70.9
(O1A, O2A, C8A–C10A)
(O1, O2, C8–C10)
(C2A–C7A)
(C2–C7)
The dioxolane conformation is described by applying
the pucker parameters according to Cremer and Pople [35],
which were obtained using the crystallographic program
PLATON [23]. A graphical summary of the parameters
and the resulting conformations is given with the help of a
so-called pseudorotation wheel (deduced from the
pseudorotation wheels of cyclopentane [36, 37] and fura-
nose [38]) in Fig. 8. Although the substitution pattern of
the dioxolane ring is similar in all five cases, molecules of
compounds 1, 2, and 3 show significant conformational
123

1138
Struct Chem (2012) 23:1131–1142
Fig. 3 Molecular structures of compounds 1, 2, and 3, showing the atom labelling schemes with displacement ellipsoids drawn at the 50%
probability level and H atoms shown as small spheres of arbitrary radii
Fig. 4 Motifs of C–HꢀꢀꢀO hydrogen bonds within a and between b molecular chains of 1. Intermolecular interactions are represented as broken
lines and non-relevant H atoms are omitted for clarity
differences in the solid state. Of the five unique dioxolane
moieties, only one adopts a twist conformation (dioxolane
1 of compound 1), while the other four have an envelope
conformation, which can be differentiated with regard to
the flap atom. In case of the terminal alkyne 2, both
molecules contain dioxolane moieties where the chiral
carbon atom C4 is out of plane. In contrast, C2 is not a part
of the dioxolane plane in compounds 1 and 3. A compar-
ison with similarly substituted dioxolanes from the litera-
ture [13–16] shows that the envelope conformation of
compound 2 with the chiral C-atom out of plane is rather
rare.
Similarities and differences of the dioxolane units can be
visualized by structural overlays (Mercury [39]). The
overlay of all dioxolane ring atoms confirms that the
dioxolane units of compounds 1 (Fig. 9a) and 2 (Fig. 9b),
respectively, are rather similar. The graphical illustration
also indicates that both dioxolane units of 1 are more
similar than the classification (molecule 1: twist, molecule
2: envelope), based on the pucker parameters, suggests.
Conformational differences between the dioxolane rings of
compounds 1 and 3, for example, are illustrated in Fig. 9c
with a comparatively high standard deviation for the
structure overlay (RMS = 0.192).
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Struct Chem (2012) 23:1131–1142
1139
Fig. 5 Intermolecular
interactions within one layer of
molecules of 2 (broken lines).
Non-relevant H atoms are
omitted for clarity
Fig. 6 Packing structure of compound 3 viewed along the a axis, showing molecular layers with enclosed crystal water (highlighted). H atoms
are omitted for clarity
The stereochemistry of the molecules can also be
described by the arrangement of dioxolane units with
respect to the phenyl ring. Only the atoms of the dioxolane
2 of compound 1 and of the corresponding phenyl ring are
almost coplanar, while the other four dioxolane units
(dioxolane 1 of compound 1, compounds 2 and 3) are
twisted relative to the plane of the aromatic spacer
(Fig. 9d–f). The greatest deviation from planarity can be
observed in case of dioxolane 1 (compound 1) with an
almost perpendicular alignment of dioxolane and phenyl
moieties. By using enantiopure (4R,5R)-diethyl tartrate as a
starting material, the stereochemistry is fixed and the
substituents in position 4 and 5 of the dioxolane ring adopt
a trans configuration. Nevertheless, there are significant
123

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Struct Chem (2012) 23:1131–1142
similar arrangement, while those in position 5 are twisted
into different directions. The carbonyl oxygen atom is
usually directed away from the dioxolane moiety, with the
exception of the dioxolane ring 1 in compound 1.
Conclusions
The new compounds (1–3) have been synthesized by
applying a sequence of acetylenic protection, Pd-catalyzed
coupling, deprotection, and transacetalization reactions
involving L(?)-diethyl tartrate in the key transacetaliza-
tion step. Using varying crystallization methods, solvent
free structures of 1 and 2 and a hydrated crystal structure
of 3 were obtained. While molecules of the tartaric ester
derivative 1 are arranged in two-dimensional strands,
compounds 2 and 3 adopt a layer structure. The data
summarized in Table 2 permit a correlation between
the strength/number of intermolecular interactions in the
crystals and the melting points of the compounds. The
solid phase structures of the esters 1 and 2 are exclusively
stabilized by weak non-conventional hydrogen bonding
comprising C–HꢀꢀꢀO and C–Hꢀꢀꢀp(arene) type interactions
which may explain the relatively low melting tempera-
tures of 74–77 and 55–59 °C, respectively. In contrast, the
presence of the water molecule in the hydrate 3 exerts a
remarkable influence on the stability of the crystal, which
is reflected by intense cross-linking of the crystal com-
ponents, including the water molecule, via O–HꢀꢀꢀO
hydrogen bonding, leading to a considerably enhanced
melting point (203–206 °C). Thus, in a way, 3 deviates
from the usual behavior of carboxylic acids forming a
hydrogen bonded dimer motif of hydrogen bonds. More-
over, a comparison of all molecular structures revealed
that the dioxolane ring adopts different conformations
(twist and envelope isomers) even though the substitution
pattern of this cyclic unit is similar in all three
compounds.
Fig. 7 Cyclic hydrogen bond network including 3 and H2O mole-
cules. Hydrogen bonds are represented as broken lines. Non-relevant
H atoms are omitted for clarity
Fig. 8 Pseudorotation wheel of 1,3-dioxolane with notifications of
corresponding pucker parameters of dioxolane units in the crystal
structures of 1 (purple), 2 (yellow), and 3 (green) (color figure online)
Supplementary data
CCDC 839596 (1), 839597 (2) and 839598 (3ꢀH2O) contain
the supplementary crystallographic data for this article.
These data can be obtained free of charge at www.ccdc.
com.ac.uk/retrieving.html [or from the Cambridge Crys-
tallographic Data Centre (CCDC), 12 Union Road, Cam-
bridge CB2 1EZ, UK; fax: ?44(0)1223-336033; e-mail:
deposit@ccdc.com.uk].
differences concerning the alignment of ethoxycarbonyl
and carboxy groups, respectively, with respect to the
dioxolane moiety. This fact can be explained by sterical
demands caused by the packing of molecules or by the
different conformations of the dioxolane rings themselves.
Figure 10 indicates that substituents in position 4 have a
123

Struct Chem (2012) 23:1131–1142
1141
Fig. 9 Structural overlays of molecular fragments of 1 (green dioxo-
lane 1, light green dioxolane 2), 2 (red molecule 1, rose molecule 2)
and 3 (blue). Fitting of dioxolane ring atoms (a–c) and phenyl ring
atoms (d–f). a RMS = 0.0402; b RMS = 0.0211; c RMS = 0.192;
d RMS = 0.0598; e RMS = 0.0277; f RMS = 0.0339 (color figure
online)
Fig. 10 Structural overlays of molecular fragments of 1 (green dioxolane 1, light green dioxolane 2), 2 (red molecule 1, rose molecule 2), and 3
(blue) by fitting dioxolane ring atoms (color figure online)
Acknowledgment Financial support from the Deutsche Fors-
chungsgemeinschaft (DFG) under the program SPP 1362/1 is grate-
fully acknowledged.
8. Rosseinsky MJ (2004) Microporous Mesoporous Mater 73:15
9. Xu R, Pang W, Yu J, Huo Q, Chen J (2007) Chemistry of
zeolithes and related porous materials. Wiley, Singapore
10. Kondo F, Iwaizumi T, Kimura H, Takeishi M (1997) Kobunshi
Ronbunshu 54:908
11. Tuzuki Y (1939) Bull Chem Soc Jpn 14:19
12. Shim YJ, Choi K (2010) Org Lett 12:880
13. Li XH, Wang DC, Liu BN, Xu W (2008) Acta Crystallogr Sect E
64:2499
14. Liu HQ, Wang DC, Xu W, Yang Z, Gai T (2009) Acta Crys-
tallogr Sect E 65:841
References
1. Pasteur L (1848) C R Hebd Seances Acad Sci 26:535
2. Latscha HP, Linti GW, Klein HA (2004) Analytische Chemie.
Springer, Berlin
3. Otto M (2006) Analytische Chemie. Wiley-VCH, Weinheim
4. Habermehl G, Hammann PE, Krebs HC, Ternes W (2008)
Naturstoffchemie. Springer, Berlin
15. Belokon YN, Gagieva SC, Sukhova TA, Dmitriev AB, Lyssenko
KA, Bravaya NM, Bulychev BM, Seebach D (2005) Russ Chem
Bull 54:2384
5. Seebach D, Beck AK, Heckel A (2001) Angew Chem 113:96
6. Zhong N, Zhao X, Ma H, Chen Y (2010) US Patent 007678
921B2
7. Kassai C, Juvancz Z, Balint J, Fogassy E, Kozma D (2000)
Tetrahedron 56:42
16. Jiang J, Pan Y, Wang DC, Ou-yang PK (2007) Acta Crystallogr
Sect E 63:1093
17. Kong SD, Luong A, Manorek G, Howell SB, Yang J (2007)
Bioconjug Chem 18:293
123

1142
Struct Chem (2012) 23:1131–1142
18. Bruker (2007) SMART, SAINT, SHELXTL, SADABS. Bruker
AXS Inc., Madison, WI
19. Sheldrick GM (2002) SADABS, Siemens Area Detector
32. Katzsch F, Eißmann D, Weber E (2011) Struct Chem. doi:
10.1007/s11224-011-9858-0]
33. Desiraju GR (1995) Angew Chem Int Ed 34:2311
34. Burrwos AD (2004) In: Mingos DMP (ed) Supramolecular
assembly via hydrogen bonds I. Structure and bonding, vol 108.
Springer, Berlin, pp 54–95
35. Cremer D, Pople JA (1975) J Am Chem Soc 97:1354
36. Lightner DA, Gurst JE (2000) Organic conformational analysis
and stereochemistry from circular dichroism spectroscopy.
Wiley, Chichester
¨
¨
Absorption Correction Program. Universitat Gottingen, Germany
20. Sheldrick GM (2008) Acta Crystallogr Sect A 64:112
21. Flack HD, Bernardinelli G (1999) Acta Crystallogr Sect A 55:908
22. Flack HD, Bernardinelli G (1999) J Appl Chem 33:1143
23. Spek AL (2009) Acta Crystallogr Sect D 65:148
24. Desiraju GR, Steiner T (1999) The weak hydrogen bond. Oxford
University Press, Oxford, UK
´
37. Cros S, du Penhoa CH, Perez S, Imberty A (1993) Carbohydr Res
25. Felsmann M, Eißmann F, Schwarzer A, Weber E (2011) Cryst
Growth Des 11:982
26. Nishio M, Umezawa Y, Honda K, Tsuboyamad S, Suezawae H
(2009) CrystEngComm 11:1757
248:81
38. Finch P (2010) Carbohydrates: structures, syntheses and
dynamics. Kluwer, Dordrecht
27. Fischer C, Lin G, Bombicz P, Seichter W, Weber E (2011) Struct
Chem 22:433
28. Boese R, Kirchner MT, Billups WE, Norman LR (2003) Angew
Chem Int Ed 42:1961
29. Salonen LM, Ellermann M, Diederich F (2011) Angew Chem Int
Ed 50:4808
30. Bernstein J, Novoa JJ, Boese R, Cirkel SA (2010) Chem Eur J
16:9047
39. Macrae CF, Bruno IJ, Chisholm JA, Edgington PR, McCabe P,
Pidcock E, Rodriguez-Monge L, Taylor R, van de Streek J, Wood
PA (2008) J Appl Crystallogr 41:466
40. Wang DC, Ge T, Wu WY, Xu W, Yang Z (2009) Acta Crys-
tallogr Sect E 65:2230
41. Wang DC, Bai J, Xu W, Gai T, Liu HQ (2009) Acta Crystallogr
Sect E 65:1960
31. Jeffrey GA (1997) An introduction to hydrogen bonding. Oxford
University Press, Oxford, UK
123